Scientists hope mouse research leads to new anti-cancer therapies

Wednesday

Oct 28, 2009 at 12:01 AMOct 28, 2009 at 12:15 PM

Can an experiment with rodents lead to the end of breast cancer as we know it? Recent collaborative work between Cambridge, Mass., research institutes has lead to a discovery of a method of screening for chemicals that selectively kills breast cancer stem cells in culture and in mice, a breakthrough that may directly or indirectly lead to new anti-cancer therapies.

Gila Babich

Can an experiment with rodents lead to the end of breast cancer as we know it?

Recent collaborative work between Cambridge, Mass., research institutes has discovered a method of screening for chemicals that selectively kill breast cancer stem cells in culture and in mice, a breakthrough that may directly or indirectly lead to new anti-cancer therapies.

“One of the major difficulties with developing good anti-cancer drugs is that the anti-cancer drugs don’t cure the tumors, and part of the reason they don’t cure the tumors is that they’re not very effective in specifically attacking and eliminating the cancer stem cells,” said Dr. Robert Weinberg, founding member of the Cambridge-based Whitehead Institute and a biology professor at MIT. “We’re trying to develop techniques to understand what creates cancer stem cells and how they are perpetuated.”

A theory prevalent amongst many researchers suggests that the aggressive subset of cancer cells -- called cancer stem cells -- drives tumor growth and causes tumors to regenerate after chemotherapy has killed 99 percent of their cells.

Isolating true-to-form cancer stem cells proved to be a challenge until recently, when researchers at Weinberg’s lab at the Whitehead Institute discovered a method to manipulate these cells.

The discovery allowed a team of scientists led by Dr. Piyush Gupta of the Cambridge-based Broad Institute to derive cell lines from human breast epithelial cells and use them to screen 16,000 chemicals in culture dishes. The scientists found that 32 of these chemicals specifically target cancer stem cells and kill them.

Gupta’s team then tested the chemical compounds in mice, and narrowed the results down to one chemical, salinomycin, that appeared to shrink tumor growth. The study was published in an August issue of the journal Cell.

“Ours was really the first step in a long process.” Gupta said. “We have one compound now, and it is not clear whether this one compound is ideal in terms of its activity and also in terms of its toxicity.”

The discovery of the potent chemical does not necessarily mean that it will have any improvement over current cancer treatment. Gupta’s team has started the extensive follow-up testing that is necessary to determine in which stage eliminating cancer stem cells would be most beneficial to patients, and whether the compound is suitable for humans at all.

“Things sometimes appear very promising in pre-clinical studies but then in patients they may for whatever reason not work as well,” Gupta said. “All we can do is try to design the best possible preclinical studies in the hope that it will work in the patients. We really want to understand how the compounds work in animals before we even think about putting them in people.”

Still, the new screening method is a promising development in the field of anti-cancer treatment. Gupta said he expects some cancer stem cell-targeting therapies to make into human trials within three to five years.

“For a while it seemed like these cancer stem cells were exciting, but there was very little known about them,” Gupta said. “Now I think that we’re finally at the stage where we can really start to understand what’s going on inside these cells.”